Formic Acid → 6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyran

HRID 1708

Reaction equation

HRID 1708 reaction equation
FC(F)(F)S(O[C:7]1[CH:46]=[CH:45][C:10]2[C:11]3[S:32][C:31]4[CH:33]=[C:34](OS(C(F)(F)F)(=O)=O)[CH:35]=[CH:36][C:30]=4[C:12]=3[CH:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:17][CH:16]=3)[O:14][C:9]=2[CH:8]=1)(=O)=O.C1(P(CCC)C2C=CC=CC=2)C=CC=CC=1.C(O)=O.C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:24]1([CH2:23][CH2:22][O:21][C:18]2[CH:17]=[CH:16][C:15]([CH:13]3[C:12]4[C:30]5[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=5[S:32][C:11]=4[C:10]4[CH:45]=[CH:46][CH:7]=[CH:8][C:9]=4[O:14]3)=[CH:20][CH:19]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 82100DiphenylpropylphosphineHCID 158713633,9-Bis(trifluoromethanesulfonyloxy)-6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyran

Product 1

HCID 107656216-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyranYield 57%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of the product of Example 6 (780 mg, 1.06 mmol), palladium(II) acetate (42 mg, 0.19 mmol), 1,2-bis(diphenylphosphinopropane (149 mg, 0.36 mmol), formic acid (0.6 mL), and triethylamine (3.0 mL) in anhydrous dimethylformamide (40 mL) was stirred at ambient temperature for 4 d. After concentration, the residue was subjected chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide). Product containing fractions were concentrated, partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL), and the aqueous layer extracted with methylene chloride (50 mL). The combined organic extracts were dried (sodium sulfate), concentrated, and the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide) to give 267 mg (57%) of the title compound as an oil which gave a white, crystalline solid, mp 107° C., upon trituration with ether/hexane: 1H NMR (300 MHz, CDCl3) d 7.86 (d, J=7.4 Hz, 1H), 7.40 (m, 1H), 7.1-7.3 (m, 6H), 6.97 (t, J=7.3 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.66 (s, 1H), 4.07 (t, J=6.1 Hz, 2H), 2.75 (t, J=6.1 Hz, 2H), 2.49 (m, 4H), 1.5-1.7 (m, 4H), 1.4-1.5 (m, 2H); 13C NMR (125 MHz, CDCl3) d 159.1, 151.6, 139.3, 137.1, 133.0, 131.5, 129.8, 129.1, 126.8, 124.6, 124.4, 123.7, 122.6, 121.5, 121.5, 119.3, 116.9, 114.6, 77.6, 65.7, 57.7, 54.9, 25.8, 24.0; MS (FD+) m/e 441 (M+); Anal. calc'd for C28H27NO2 S: C, 76.15; H, 6.17; N, 3.17. Found: C, 75.93; H, 6.44; N, 3.01.

Workup

  1. concentrationAfter concentration
  2. additionProduct containing fractions
  3. concentrationwere concentrated
  4. custompartitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL)
  5. extractionthe aqueous layer extracted with methylene chloride (50 mL)
  6. dry with materialThe combined organic extracts were dried (sodium sulfate)
  7. concentrationconcentrated
  8. customthe residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-37dabead809445b0a1f66e1d5ecbac91
Source dataset
uspto-grants-1998_03
Patent number
US05726186

Linked notes

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